The levels of cyclic nucleotides were determined in both cerebellum and cerebral cortex following either pharmacological treatment or during electrically-induced seizures. Generally, neurotropic agents which either depress the CNS or protect against seizures decrease cerebellum cyclic GMP and agents which stimulate the CNS increase the cyclic GMP. Cyclic AMP is not pharmacologically responsive in either region. Electroconvulsive shock increases the levels of both cyclic nucleotides in both the cerebellum and the cerebral cortex. However, there is a temporal disparity in the cyclic nucleotide responses which favors the concept that the two cyclic nucleotides have separate and distinct roles in the CNS.